Cryosurgery is a common and effective surgical procedure in which freezing is used to destroy undesirable tissue. The procedure is used in many areas of medicine such as dermatology, gynecology, otolaryngology, proctology, veterinary medicine. In cryosurgery, freezing is usually accomplished by placing a metallic cryosurgical probe, insulated except at its tip, in contact with the subject tissue to be frozen. As the probe is cooled internally (by either circulating a refrigerant (cryogen), Joule Thompson effects, Peltier effects, or by means of heat pipes) heat is removed from the tissue by conduction and a region of frozen tissue grows outward from the probe. When an adequate amount of tissue has been frozen, the flow of cryogen is stopped and the tissue is allowed to thaw.
One of the advantages of cryosurgery is that it can treat tumors focally. Small volumes can be destroyed using a thin needle-like cryosurgical probe, while larger volumes can be destroyed with larger probes or multiple probes. Multiple sites may be treated in this manner and irregularly-shaped volumes can be treated using multiple probes. Retreatment is possible if the disease recurs.
Because tissues can be treated focally, cryosurgery has the potential to spare more adjacent healthy tissue than resection, radiotherapy, or hyperthermia. Another advantage of cryosurgery is that it is easy to control because the freezing process is relatively slow, usually on the order of 1 mm/min. If the therapy is adequately monitored, freezing can be halted before the freezing interface reaches sensitive tissues. An additional advantage of the slow freezing rate of cryosurgery is that capillaries freeze while larger vessels, which act as local heat sources, remain undamaged. Cryosurgery is therefore effective in treating otherwise unresectable solid tumors abutting large blood vessels.
Cryosurgery has also been successfully used in the treatment of many benign and malignant skin cancers. [Torre, D., "Cryosurgery of Basal Cell Carcinoma," Journal of the American Academy of Dermatology, 1986; 15(5):917-29.][Breitbart][Kuflik, A., et al., "Lymphocytoma Cutis: A Series of Five Patients Successfully Treated with Cryosurgery," Journal of the American Academy of Dermatology, 1992; 26:449-52][Tappero, J.W., et al., "Cryotherapy for Cutaneous Kaposi's Sarcoma (KS) Associated with Acquired Immune Deficiency Syndrome (AIDS); A Phase II Trial," Journal of Acquired Immune Deficiency Syndromes, 1991; 4(9):83946][Dachow-Siwie'c, Elzbieta, "Treatment of Cryosurgery in the Premalignant and Benign Lesions of the Skin," Clinics in Dermatology 1990; 8(1):69-79]. For lesions which are less than 3 mm in depth and benign, the recommended treatment is a liquid nitrogen spray, open or constrained by a neopreme cone barrier or otoscope cone [Torre, D., "Cryosurgery of Basal Cell Carcinoma," Journal of the American Academy of Dermatology, 1986; 15(5):917-29.]]. The depth and lateral extent of the cryolesion is estimated by the surgeon to be some percentage of the lateral spread of the frozen region at the surface [Torre, D., "Cryosurgery of Basal Cell Carcinoma," Journal of the American Academy of Dermatology, 1986; 15(5):917-29]. However, for tumors which are deeper than 3 mm, or for malignant tumors, some surgeons prefer a closed probe. It is recommended that some type of instrumentation be used during surgery in order to monitor the depth dose. Thermocouple tipped hypodermic needles are the most common method of instrumentation, but ultrasound and electrical resistance/impedance measurements have also been used. Though thermocouple measurements are the most common, they give the surgeon only a rough idea of the zone of cold injury based on one or more discrete measurements. Single point measurements may be an ineffective measure of the depth of the dose due to variations in fat content and thus the local tissue thermal conductivity, increased blood flow in the region near the cryolesion [Bircher, A.J., Buchner, S.A., "Blood Flow Response to Cryosurgery on Basal Cell Carcinomas," Acta Derm Venereol (Stockholm) 1991; 71:531-3] or heat sources presented by medium sized blood vessels.
MRI has been shown to be useful in determining skin lesion depths, and is recommended by Zemtsov et. al. for preoperative evaluation of lesions [Zemtsov, A., et al., "Magnetic Resonance Imaging of Cutaneous Neoplasms: Clinicopathologic Correlation," Journal of Dermatological Surgery and Oncology, 1991;17:416-22; Zemtsov, A., et al., "Magnetic Resonance Imaging of Cutaneous Melanocytic Lesions," Journal of Dermatological Surgery and Oncology, 1989; 15:854-58]. Zemtsov and colleagues have demonstrated that several types of lesions can be successfully imaged using a commercially available General Electric brand 1.5 Tesla NMR spectrometer, and have shown that NMR calculated tumor depths correlate well with Breslow's measured depths.
The idea of using cold in medical therapeutics has been documented as early as the third century BC but its use in treating tumors was first attempted successfully during the last century by James Arnott. Contemporary cryosurgery can be traced to the early 1960's when Cooper and Lee developed a cryosurgical apparatus consisting of a hollow metal tube, vacuum insulated except at its tip, through which liquid nitrogen flowed [Ablin, R.J., Handbook of Cryosurgery, Marcel Dekker Inc., New York, 1980]. They treated Parkinsonism by freezing the basal ganglia until the patient's tremor subsided. Although the treatment was effective in providing palliation, it was replaced by drug therapy when L-Dopa became clinically available. During the sixties and early seventies the cryosurgical treatment of skin lesions and lesions of other tissues outside the body provided satisfactory results [Gage, A., "Current Progress in Cryosurgery," Cryobiology 25:483-486, 1988. Rubinsky, B., Onik, G., "Cryosurgery: Advances in the Application of Low Temperature to Medicine," International Journal of Refrigeration, 14: 1-10, 1991. However, enthusiasm waned for the technique after initial attempts to treat tumors deep in the body. The reasons for the reduction in interest in cryosurgery are due to two problems faced by surgeons:
1) Since the frozen region propagates from the probe into opaque tissue it is impossible to visually monitor the extent of the frozen region. This can result in either insufficient freezing, leaving undesirable tissues unfrozen, or too much freezing which can damage essential tissues.
2) Since freezing itself does not always result in tissue damage, it is difficult to estimate how much of the frozen tissue is actually destroyed.
Understandably, surgeons have been reluctant to use a technique in which they are unable to observe and control the immediate consequences of their actions. However, the latest advances in imaging technology have the potential for overcoming the two problems noted above. In fact, intraoperative ultrasound technology has already facilitated cryosurgery in the liver and prostate with good results [Onik, G., Ruinsky, B., Zemel, R., Weaver, L., Diamond, D., Cobb, C., Porterfield, B., "Ultrasound Guided Hepatic Cryosurgery in the Treatment of Metastatic Colon Carcinoma; Preliminary Results," Cancer 67:901-907, 1991. Onik, G., Porterfield, B., Rubinsky, B., Cohen, J., "Percutaneous Transperineal Prostate Cryosurgery Using Transrectal Ultrasound Guidance: Animal Model," Urology 37:277-281; 1991.] However, ultrasonic monitoring of cryosurgery which utilized the reflected pressure waves from the freezing interface has drawbacks. First, ultrasound only provides a planar section of the three-dimensional ice front. Second, the region behind the freezing interface (which reflects the pressure waves) is in shadow and cannot be observed. In the liver, this problem can be overcome by moving the ultrasound transducer to a different location to obtain a different point of view. However, imaging of the prostate is only possible from a limited number of sites. Irregular ice structure in the prostate hidden from the ultrasonic monitoring can result in complications such as urethrorectal or urethrocutaneous fistulas. Third, many organs such as the brain are not easily accessible to ultrasound. Fourth, ultrasound shows only the position of the freezing interface, but does not provide information concerning the extent of tissue damage.
Nuclear Magnetic Resonance (NMR) monitoring of cryosurgery can circumvent many of the above-mentioned problems. NMR works by putting the sample in a strong static magnetic field, applying a transient magnetic field to the nucleus of atoms in a target region and recording the radio frequency signals emitted as they revert to their unexcited state. The frequency is a function of the atom excited, the positional and orientational relation between the atom and its neighbors in a particular molecule and the local applied field. Therefore the emitted signal can be used to determine the presence of certain atoms and their chemical environment. The intensity of the signal can be correlated to the amount of the investigated species present. Other factors also affect the signal emitted, such as temperature or thermodynamic state. Some of the most important species studied in biological NMR are protons, phosphorous, sodium, and carbon. NMR imaging can be used to monitor freezing during cryosurgery and to optimize the cryosurgical procedure. NMR spectroscopy and spectroscopic imaging can also provide information concerning the relation between tissue that was frozen and tissue that is damaged.
MR imaging (MRI) is a promising tool for assisting cryosurgery for several reasons:
1. Prior to surgery, anatomical information of the region to be frozen can be obtained from MRI and used in cryosurgical treatment planning. The information can be used to model the freezing process and calculate the optimal number of cryoprobes to use, the locations they should be placed at, and the optimal freezing protocol. These procedures can be performed not only with images from MRI but also with images from ultrasound CT, PET and other imaging techniques.
2. Fast, multiple-slice MRI can provide three or more planes acquired in less than 60 seconds, and can provide three-dimensional images of the frozen region during cryosurgery. This provides adequate time resolution to follow the freezing process and to make treatment protocol decisions. MRI imaging can be used to monitor the extent of freezing since ice is invisible under proton NMR while unfrozen tissue is not. The transition of water from liquid to solid is accompanied by large decreases in the proton NMR signal from the water since interactions that are averaged to near zero by molecular tumbling in the liquid (motional narrowing) become significant in the solid thereby increasing relaxation rates by orders of magnitude. This makes water protons in ice invisible to standard NMR imaging techniques and frozen regions appear black [Isoda, H., "Sequential MRI and CT Monitoring in cryosurgery--an experimental study in polyvinyl alcohol gel," Panthom Nippon Igeku Hoshagen Gakkai Zasshi, Nippon Acta Radiologica, 49:1096-1001, 1589 (in Japanese). Isoda, H., "Sequential MRI and CT monitoring in cryosurgery--an experimental study in rats," Nippon Acta Radiologgia, 49:1499-1508, 1989].
The minimum requirement for monitoring cryosurgery is that the position of the freezing interface be ascertainable. Thus almost any NMR imaging method may be employed, including fast and ultra-fast methods such as Fast Low-Flip Angle NMR (FLASH), echo-planar NMR, and radio frequency spoiled gradient echo, i.e. a FLASH sequence with the transverse coherence spoiled by randomizing phase radio frequency pulses. [Cohen, M.S., and Weisskoff, R.H., "Ultra-fast Imaging," Magnetic Resonance Imaging 9, 1-37 (1991). Zur, Y., Wood, M., and Neuringer, L., "Spoiling of Transverse Magnetization in Steady State Sequences," Magnetic Resonance Medicine 21, 251-263 (1991)].
3. Real-time NMR imaging can provide information on the state of the tissue in and around the freezing interface such as the position of the freezing interface, its velocity, the temperature distribution in the unfrozen region, and the temperature distribution in the unfrozen region. The temperature distribution in the unfrozen region can be found, for example, from T1-weighted Inversion Recovery Rapid Acquisition with Relaxation Enhancement (IR-RARE) sequences [Dickinson, R.J., Hall, A.S., Hind, A.J., Young, I.R., "Measurement of Changes in Tissue Temperature using MR Imaging," Journal of Computer Assisted Tomography, 1986:10; 468-472], and other techniques [Le Bihan, D., Delannoy, J., Levin, R.L., "Temperature Mapping with MR imaging of Molecular Diffusion: Application to Hyperthermia," Radiology 1589:853-857], and [Rubinsky, B., Gilbert, J.C., Onik, G.M., Roos, M.S., Wong, S.T.S., Brennan, K.M., "Monitoring Cryosurgery in the Brain and in the Prostate with Proton NMR," Cryobiology, April 1993], and the temperature distribution in the frozen region can be calculated knowing the position of the interface and the temperature of the probe as was done with ultrasound [Gilbert, J.C., Rubinsky, B., Onik, G.M., "Solid-Liquid Interface Monitoring with Ultrasound During Cryosurgery," ASME paper #85-WA/HT-83, 1985]. This information can be used to adjust and control the freezing process in situ, either by providing information to the surgeon or in an automated control system.
4. Post-cryosurgical MR follow-up provides a noninvasive means of determining the efficacy of treatment. T2-weighted MRI can track the evolution of edema and other changes in and around the tissue treated with cryosurgery over periods of minutes to days [Vining, E., Duckwier, G., Udkoft, R., Rand, R., Lufkin, K., "Magnetic Resonance Imaging of the Thalamus Following Cryothalamotony for Parkinson's Disease and Dystonia," Journal of Neuroimaging, 1, 196-198 (1991); Rubinsky, B., Gilbert, J.C., Onik, G.M., Roos, M.S., Wong, S.T.S., Brennan, K.M., "Monitoring Cryosurgery in the Brain and in the Prostate with Proton NMR," in print, Cryobiology, 1993]. T1-weighted MRI can detect bleeding and changes in the state of any post-cryosurgical hemorrhage. With the use of contrast agents such as Gd-DTPA (gadopentetate dimeglumine), T1-weighted MRI can also delineate the region of blood-brain barrier disruption after freezing as will be discussed below. Furthermore, spectroscopy and spectroscopic imaging of phosphorous, carbon, and sodium are also useful in determining the extent of tissue damage after cryosurgery. In the case of sodium, it is the ratio between the intracellular to extracellular sodium which are indicative of damage. In the case of phosphorous, it is the molecular composition, and the relative composition in which the compound appears as, ATP, ADP, phosphocreatine or inorganic phosphorous which indicates the extent of the damage.
In summary, NMR imaging can be used in four differeilt stages during cryosurgery to improve the results of the procedure: 1) in the preoperative stage in a predictive mode to plan the procedure and optimize the application of cryosurgery; 2) during cryosurgery to image the process of freezing; 3) for interactive control during the surgery to control and optimize the application of cryosurgery; and 4) in the post-operative stage to evaluate the damage induced by the procedure.
Despite the advantages of MRI, the efficient use of MRI with cryosurgery is inhibited by the nature of the MRI apparatus and limitations of the technique. In particular:
1) MRI operates in a magnetic environment and employs radio frequency electromagnetic energy. Consequently conventional metallic cryosurgical probes cannot be used with MRI. Experiments reported by other groups were limited to the use of a gauze immersed in liquid nitrogen and then applied to the skin [Isoda, H., "Sequential MRI and CT Monitoring in Cryosurgery--an Experimental Study in Rats," Nippon Acta Radiologica, 49:1499-1508, 1989 (in Japanese)], or to the use of a styrofoam cup filled with liquid nitrogen [Matsumoto, R., Oshio, K., Jolesz, F., "Monitoring of Laser and Freezing Induced Ablation in the Liver with T1--Weighted MR Imaging," Journal of Magnetic Resonance Imaging, 2, 555-562, 1992]. The present invention relates to the design of a cryosurgical probe compatible with MRI.
2) It is preferable for MR imaging that the region imaged be stationary with respect to the magnet. The present invention is therefore a stereotactic apparatus for positioning cryosurgical probes in relation to the MRI apparatus.
3) During cryosurgery the region of interest that is frozen and imaged is usually small relative to the whole region imaged by MRI. This is particularly the case in dermatology where freezing penetrates only a few millimeters from the probe. The present invention is therefore directed to a cryosurgical probe on which the radio frequency coil of the MRI system is attached. This generates a much higher signal to noise ratio in the region of interest, with a much higher resolution (of about 100 .mu.m). This is an optimal solution, since the cryosurgical probe is naturally in the center of the region of interest. Another advantage of mounting the coil on the probe is that it is then possible to construct a probe where the cryogen also cools the coils, thereby reducing thermal noise and increasing the signal-to-noise ratio still further.
4) The low signal intensity of atomic species other than protons makes the signal-to-noise ratio of these species (such as phosphorus or sodium) very low. Attaching a receiver coil tuned to these species to the cryosurgical probe is advantageous since the signal/noise ratio is significantly improved by analyzing only the area of interest. Furthermore the cryosurgical probe is by the nature of its function in the center of the region of interest.
Attaching the MR receiving coil to the cryosurgical probe provides the advantages of increased resolution in the area of interest during cryosurgery, and increased ability to determine the effectiveness of cryosurgery, without the need for introducing additional devices in the patient. Such an arrangement may also be useful with other microsurgical techniques, such as laser surgery, or mechanical resection.
The advantage of an MRI assisted microsurgical system is that it can provide a better resolution in the region treated by various surgical techniques and it can be used to better monitor tissues during surgery. Furthermore, since it involves only the attachment of small electric components to the surgical device, it does not substantially increase the bulk of the device. This technique can remove the need for optical imaging of surgical procedures using fiber optics, thereby facilitating surgery with smaller devices and in smaller areas.
The present invention relates generally to methods and apparatus for improving the results of cryosurgery, and more particularly to methods and apparatus for improving the results of cryosurgery using preoperative surgical optimization planning, real-time NMR imaging during surgery, control of the cryosurgical procedure using NMR image information, and/or post-operative NMR monitoring of cryodamage.
An object of the present invention is to provide methods and apparatus for improving cryosurgical results.
Another object of the present invention is to provide methods and apparatus for improving cryosurgical results using preoperative surgical planning in combination with MR image information.
Another object of the present invention is to provide methods and apparatus for improving surgical results, particularly cryosurgical results, using real-time NMR imaging during surgery.
Another object of the present invention is to provide methods and apparatus for improving cryosurgical results by controlling the cryosurgical procedure using real-time NMR image information.
Another object of the present invention is to provide methods and apparatus for postoperative NMR monitoring of cryodamage.
,Another object of the present invention is to provide methods and apparatus for utilizing the heat and mass transfer equations in the preoperative planning stage and during surgery to improve cryosurgical results.
Another object of the present invention is to provide methods and apparatus for determining tissue temperatures using NMR data to improve cryosurgical results.
Another object of the present invention is to provide methods and apparatus for determining tissue temperatures by solving the heat and mass transfer equations in the frozen region.
Another object of the present invention is to provide methods and apparatus for improving cryosurgical results using an MR compatible cryoprobe and stereotactic device.
Another object of the present invention is to provide methods and apparatus for improving cryosurgical results by increasing the resolution of MR monitoring using an MR coil mounted on the cryoprobe.
Another object of the present invention is to provide methods and apparatus for evaluating cryosurgical results using NMR spectroscopy and imaging, such as phosphorous-31 or sodium-23 spectroscopy and imaging.
Additional objects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and obtained by means of the instrumentalities and combinations particularly pointed out in the claims.